ERBITUX™ (Cetuximab) is a recombinant, human/mouse chimeric monoclonal antibody manufactured by ImClone Systems Incorporated and distributed and marketed by Bristol-Myers Squibb Company. 3% of patients receiving ERBITUX™ (Cetuximab) have an adverse reaction to the drug. 90% of the severe reactions are associated with initial drug infusion. Adverse reactions include rapid onset of airway obstruction (including anaphylaxis.)
Recombinant monoclonal antibodies (mAb) are playing an increasing role in the management of many diseases including malignancies, inflammatory bowel disease, rheumatoid arthritis, and asthma (1, 2, 3). While these agents are generally well tolerated, hypersensitivity reactions (HSR) occur and can be both rapid and severe (4, 5, 6, 7). Cetuximab, a chimeric (mouse/human) IgG1 mAb against the epidermal growth factor receptor (EGFR) is approved for use in patients with metastatic colorectal cancer (CRC) and head and neck squamous cell carcinoma (HNSCC) (2,6,8,9,10). According to the Drug Product Label, severe HSR to cetuximab occur in 3% of cases. However, higher rates and clusters of cases have been reported from North Carolina, Arkansas, Missouri, Virginia and Tennessee (6,9,11). A recent publication reported that 22% of patients treated with cetuximab in Tennessee and North Carolina had severe HSR (11). By contrast, rates of HSR are lower (<1%) in most centers in the northeast. Review of the case reports on HSR to cetuximab revealed that many occurred within minutes of first exposure to the drug and were compatible with IgE mediated anaphylaxis (12,13).
There is a long felt need in the art for methods helpful in predicting whether a subject will react adversely to treatment with a protein such as cetuximab. The present invention satisfies this need.